Brain cell death is reduced with cooling by 3.5°C to 5°C but increased with cooling by 8.5°C in a piglet asphyxia model.
Brain cell death is reduced with cooling by 3.5°C to 5°C but increased with cooling by 8.5°C in a piglet asphyxia model.
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DOI：
10.1161/strokeaha.114.007330
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发表时间：
2015-01
期刊：
影响因子：
8.3
通讯作者：
Robertson NJ
中科院分区：
文献类型：
--
作者：
Alonso-Alconada D;Broad KD;Bainbridge A;Chandrasekaran M;Faulkner SD;Kerenyi Á;Hassell J;Rocha-Ferreira E;Hristova M;Fleiss B;Bennett K;Kelen D;Cady E;Gressens P;Golay X;Robertson NJ
在患有中度至重度新生儿脑病的婴儿中，全身冷却至33-34°C持续72小时是标准护理，需要进行治疗以防止6-7个不良结局。提供最佳神经保护的精确大脑温度是未知的。在定量的全脑缺氧-缺血损伤后，将28只<24小时的仔猪随机分配（每组n=7）：（i）正常体温（始终为38.5 ℃），或损伤后2-26小时全身冷却至（ii）35 ℃、（iii）33.5 ℃或（iv）30 ℃。在损伤后48小时，评估延迟的细胞死亡（TUNEL和裂解的半胱天冬酶3）和小胶质细胞衍生物（Iba-1）。伤后48 h，常温组和30° C低温组均出现明显的脑损伤。然而，在35°C和33.5°C冷却下，在大多数脑区域中观察到延迟细胞死亡和小胶质细胞活化的明显减少（P<0.05），35°C和33.5°C冷却组之间没有差异。在室周白色物质、尾状核、壳核、海马和丘脑的延迟性细胞死亡中观察到保护模式，具有U形温度依赖性。室周白色质、尾状核、内囊和海马的小胶质细胞激活模式呈倒U型温度依赖性（均P<0.05）。冷却至35°C（如治疗性低温方案中的3.5°C的绝对下降）或冷却至33.5 °C在新生仔猪脑缺氧缺血损伤后的大部分脑区域中提供保护。虽然相对较宽的治疗范围（3.5-5°C的温度下降）令人放心，但过度冷却（8.5°C的下降）显然对某些大脑区域有害。
In infants with moderate to severe neonatal encephalopathy, whole body cooling to 33-34°C for 72 hours is standard care with a number needed to treat to prevent one adverse outcome of 6-7. The precise brain temperature providing optimal neuroprotection is unknown. After a quantified global cerebral hypoxic-ischemic insult, 28 piglets aged <24h were randomized (each group n=7) to: (i) normothermia (38.5°C throughout), or whole-body cooling 2-26 h post-insult to (ii) 35°C, (iii) 33.5°C or (iv) 30°C. At 48h post-insult, delayed cell death (TUNEL and cleaved caspase 3) and microglial ramification (Iba-1) were evaluated. At 48h post-insult, substantial cerebral injury was found in the normothermia and 30°C-hypothermia groups. However, with 35°C and 33.5°C cooling, a clear reduction in delayed cell death and microglial activation was observed in most brain regions (P<0.05), with no differences between 35°C and 33.5°C cooling groups. A protective pattern was observed, with U-shaped temperature dependence in delayed cell death in periventricular white matter, caudate nucleus, putamen, hippocampus and thalamus. A microglial activation pattern was also seen, with inverted U-shaped temperature dependence in periventricular white matter, caudate nucleus, internal capsule and hippocampus (all P<0.05). Cooling to 35°C (an absolute drop of 3.5°C as in therapeutic hypothermia protocols) or to 33.5 °C provided protection in most brain regions after a cerebral hypoxic-ischemic insult in the newborn piglet. While the relatively wide therapeutic range of a 3.5-5°C drop in temperature was reassuring, overcooling (an 8.5°C drop) was clearly detrimental in some brain regions.